Enhancement of hepatic drug biotransformation rate by polychlorinated biphenyls in rats FED cholesterol-rich diet

A combined effect of cholesterol and polychlorinated biphenyls (PCBs) on the microsomal drug hydroxylation and glucuronidation in the liver of the rat was studied. PCBs, Clophen A-50 and A-60, having an average chlorination degree of 50 and 60% affect the structure of microsomal membranes. It was found that Clophen A-60 increased the binding of trypsin- and digitonin-sensitive proteins to the membranes. Also it was found that PCBs enhanced the phospholipid content of microsomes. PCBs increased the activity of hepatic NADPH cytochrome c reductase about 1.5-fold. Aryl hydrocarbon hydroxylase activity doubled with Clophen A-50 and quadrupled with Clophen A-60. Hepatic UDPglucuronosyltransferase activity was doubled with both PCBs. The enhancement in hepatic aryl hydrocarbon hydroxylase and in UDPglucuronosyntransferase was found to be lower in the presence of high cholesterol level in the diet when compared to earlier results. This is supposed to be due to the membraneous effects of cholesterol.     

Visual Acuity and Mortality in Older People and Factors on the Pathway

Purpose: To examine vision as a predictor of mortality in older people and the role of mobility, depressed mood, chronic diseases, body mass index, physical activity and injurious accidents in this possible association. Methods: 223 persons aged 75 and 193 persons aged 80 years at the baseline participated in visual acuity measurements. Visual acuity (VA) of < 0.3 in the better eye was defined as visual impairment, VA of ≥ 0.3 but ≤ 0.5 as lowered vision and VA > 0.5 as normal VA. Death dates were received from the official register. Cox regression models were used to determine the relative risks of mortality and to study what factors lie on the pathway from poor vision to mortality. Results: Over the 10-year follow-up, 107 (48%) persons aged 75 years and 138 (72%) aged 80 years at the baseline died. The risk for mortality among the 75-year-olds with lowered vision was 1.98 (95 % CI 1.25–3.13) and with visual impairment 1.90 (95% CI 1.12–3.20) compared to those with normal VA. Lower walking speed, physical inactivity, cardiovascular diseases, injurious accidents, diabetes and depressed mood each attenuated the risk markedly. Nevertheless, lowered vision remained a significant predictor of mortality even after including all these variables in the model. Among the 80-year-olds vision did not correlate with mortality. Conclusions: Lowered vision and severe visual impairment predicted mortality in the 75-year-old but not 80-year-old population. The increased risk was partially explained by lower walking speed, physical inactivity, cardiovascular diseases, depressed mood, diabetes and injurious accidents.     

Mobility limitations and cognitive deficits as predictors of institutionalization among community-dwelling older people

PURPOSE: Mobility limitations and cognitive disorders have often been observed as risks for institutionalization. However, their combined effects on risk of institutionalization among initially community-dwelling older people have been less well reported. DESIGN: A prospective cohort study with 10-year surveillance on institutionalization. SUBJECTS: Study population (n = 476) consisted of 75- and 80-year-old people who were community-dwelling, had not been diagnosed with dementia, and participated in tests on walking speed and cognitive capacity at a research centre. MEASURES: Cognitive capacity was measured with three validated psychometric tests that were from the Wechsler Adult Intelligence Scale, Wechsler Memory Scale and Schaie-Thurstone Adult Mental Abilities Test. Mobility was measured with walking speed over a 10-m distance. Exclusive distribution based study groups were formed with cut-offs at the lowest third as follows: no limitation, solely mobility limitation, solely cognitive deficits, and combined mobility limitation and cognitive deficits. Cox proportional hazards model was used to determine the relative risks of institutionalization for the study groups. RESULTS: Eleven percent of the participants were institutionalized during the 10-year surveillance. The risk for institutionalization was 4.9 times greater (95% confidence interval: 2.1-11.2) for those who had co-existing mobility limitations and cognitive deficits than for those with no limitations. CONCLUSIONS: The findings show that the accumulation of limitations in physical and cognitive performance substantially decreases the possibility for a person remaining at home. This might be due to a decreased reserve capacity and ineffective compensatory strategies. Therefore, interventions targeted to improve even one limitation, or prevent accumulation of these risk factors, could significantly reduce the risk of institutionalization.     

Associations of socio-economic position and disability among older women in Britain and Jyväskylä, Finland

The aim was to compare the pattern of associations in measures of socio-economic position and disability among British and Finnish older women. In Britain data from the British Women's Heart and Health Study was used. Women from 23 towns took part in a nurse-assessed medical examination and postal questionnaire (n = 4286). In Finland, data from the Evergreen study was used. Eight hundred and four women from the city of Jyv?skyl? were interviewed at home. Socio-economic position was measured according to social class in childhood, education, use of a car, home ownership and previous occupation. Disability measures included questions on difficulties in washing/dressing and climbing stairs. Logistic regression analyses were conducted to examine the relationship between disability and socio-economic position. In the age-adjusted analysis of both samples increasing disability in washing/dressing and climbing stairs was associated with at least one of the measures of deprivation. The relationship between socio-economic position and disability was more distinct in the British than Finnish women. Despite adjustment for a range of confounders, the relationship between socio-economic position and disability was not much attenuated, particularly in the British women. The associations in the measures of socio-economic position and disability showed a slightly different pattern between the British and Finnish women.     

Muscle strength according to level of physical exercise and educational background in middle-aged women in Finland

Summary The aim of this study was to examine the role of socio-economic status and the practice of physical exercise in explaining variation in muscle strength in 50 to 60-year-old women. Consequently, four study groups combining education and physical activity were formed: (1) university education, physically active; (2) university education, sedentary; (3) vocational or lower level of education, physically active; (4) vocational or lower level of education, sedentary. Maximal isometric strength of hand grip, arm flexion, body flexion and extension as well as dynamic power of the abdominal muscles were measured in 112 women. The results of the maximal isometric strength measurements were standardised by body mass index. The means of the maximal isometric strength results and sit-up tests were compared between the groups using two-way analysis of variance. The physically active women performed better than the sedentary in both the isometric and dynamic tests. Greater muscle strength was also found among the more highly educated compared with the less educated. The less educated sedentary women showed the poorest performance in the strength tests.     

Oral Health-Related Quality of Life among Parents and Teachers of Disabled Schoolchildren in Kuwait

Objective

The objective of this study was to assess the oral health-related quality of life between the parents and the teachers of disabled schoolchildren in Kuwait.

Subjects and Methods

The three category response version of the General Oral Health Assessment Index (GOHAI) (12 questions, always, sometimes, never) was used in the questionnaires in Kuwait. Three hundred and eight (308) parents and 112 teachers were enrolled in this study.

Results

The mean age of the parents was 45 ± 9.9 years and of the teachers 38 ± 8.4 years. The mean GOHAI was 27.2 ± 3.5 among the parents and 27.8 ± 3.3 among the teachers (p = 0.091). GOHAI was higher in the older age groups (p = 0.002) and among the parents with a university education (p < 0.001). GOHAI was also higher with increasing toothbrushing frequency among the parents (p = 0.047) and the teachers (p = 0.003). Altogether, 203 (66%) of the parents and 85 (76%) of the teachers were always able to swallow comfortably; 123 (40%) of the parents and 41 (37%) of the teachers were able to eat without discomfort. Overall, 132 (43%) of the parents and 41 (37%) of the teachers were always pleased and happy with the looks of their teeth and gums, or dentures. The Cronbach''s alpha (0.83) indicated a high degree of internal consistency between different GOHAI items.

Conclusion

There seemed to be no difference in the impact of oral health on the quality of life between the parents and the teachers of disabled schoolchildren. Oral health had a relatively weak impact on the quality of life of these adults.Key Words: Quality of life, GOHAI, Parents, Teachers, Disabled children     

Enhanced metabolic activation of chemical hepatocarcinogens in woodchucks infected with hepatitis B virus

The metabolism of chemical carcinogens was investigated in liverpreparations from 28 captive woodchucks (Marmotamonax). Of these,23 were naturally infected with the wood-chuck hepatitis virus(WHV), and eight also had primary hepatocellular carcinoma (PHC).Twenty-nine parameters were investigated in liver subcelhilarfractions, including cross-reactivity with HBsAg, and biochemicalparameters, such as -glutamyl transpeptidase, cytochrome P-450and mirosomal monooxygenases (aryl hydrocarbon hydroxylase,ethodycoumarin and ethoxyresorufin deethylases, amino-pyrineand dimethylnitrosamine demethylases, and testosterone 7-and16ß- and 6ß-hydroxylases), uridine 5'-diphos-phoglucuronosyltransferase, GSH and related enzymes (peroxidase, reductaseand S-transferase), as well as other cytosolic enzyme activities(glucose 6-phosphate and 6-phosphogluconate dehydrogenases,NADPH- and NADH-dependent diaphorases, and DT diaphorase). Inaddition, liver preparations were used in order to quantifythe metabolic activation into bacterial mutagens of five procarcinogens(aflatoxin B¹, the pyrolysis products Trp-P-2 and MelQ, 2-aminofluoreneand dimethylnitrosamine) and the decrease of potency of threedirect-acting mutagens (sodium di-chromate, ICR 191 and 4-nitroquinoline1-oxide). WHV infection produced a significant stimulation ofcarcinogen metabolism, as shown by the simultaneous change indetoxification parameters (GSH depletion) and activation indices(enhancement of microsomal monooxygenases and of pro-carcinogenactivation into mutagenic metabolites). There were no significantdifferences between WHV-positive samples from animals, withoutPHC and the noncancerous tissue of PHC-bearing animals, whereasa decrease of both activation and detoxification indices wasrecorded in the turmorous tissue. There was a considerable interindividualvariability among WHV carriers, which was tentatively ascribedto genetic factors. Pregnancy was the only known factor influencingthe results in WHV carriers. However, even by excluding pregnantanimals, the effects on carcinogen metabolism produced by WHVinfection were still statistically significant. These results,together with previous data obtained in humans, revealed thatmetabolic factors may play a role in the synergism between viralhepatitis and chemical hepato-carcinogens in the etiopathogenesisof PHC.     

Immunochemical characterization of cytochrome P-450 isozymes responsible for benzene oxidation in the rat liver

The contribution of cytochrome P-450 isozymes to benzene metabolismin liver microsomes from fed, fasted, pyrazole-, pbenobarbital(PB)- and ethanol-treated rats and in respective isocaloriccontrols was investigated using monoclonal antibodies (mAbs).Clone 1-7-1 mAb did not inhibit benzene metabolism, whereasclone 2-66-3 inhibited only in PB-induced microsomes at a highconcentration of benzene (6.26 mM), and clone 1-91-3 mAb inhibitedbenzene metabolism in all cases. The degree of inhibition wasas follows: fed isocaloric control PB < fasted < pyrazole ethanol. The pattern of inhibition was similar with clone 1-91-3for low (0.23 mM) and high concentrations of benzene, exceptin PB-induced mkrosomes. Western blot analysis showed that clone1-7-1 mAb did not bind any liver mkrosomal protein in the regionof cytochrome P-450s, whereas with clone 2-66-3 a clear-cutband was seen only in liver microsomes from PB-treated rats,with clone 1-98-1, a band was detected in mkrosomes from alltreated groups, in the following order: PB = isocaloric control< fed < fasted < pyrazole < ethanol. These resultsindicate that (i) cytochromes P-450b,e and P-450J contributeto benzene metabolism in rat liver; (ii) the former has a lowaffinity to benzene and is induced by PB; and (iii) P-450J hasa high affinity to benzene and is induced by 1-day fasting,pyrazole and ethanol, but decreased by PB treatment.     

Hypolipidemia and peroxisome proliferation induced by phenoxyacetic acid herbicides in rats

Male Wistar rats were treated daily by gavage with two phenoxy herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D)(100-200 mg/kg body wt) and 4-chloro-2-methylphenoxyacetic acid (MCPA) (100-200 mg/kg body wt), and with the chemically different glyphosate N-phosphonomethyl glycine (300 mg/kg body wt) 5 days per week for 2 weeks. A hypolipidemic drug, clofibrate [ethyl-2-(4-chlorophenoxy)-2-methylpropionate], which is structurally related to phenoxy acids, was used as a positive control (200 mg/kg body wt). 2,4-D and MCPA had several effects similar to those of clofibrate: all three compounds induced proliferation of hepatic peroxisomes, decreased serum lipid levels, and increased hepatic carnitine acetyltransferase and catalase activities. 2,4-D and MCPA, but not clofibrate, decreased lipoprotein lipase activity in the adipose tissue to about a third of the control value but did not change the lipoprotein lipase activity in the heart muscle. The data suggest that these compounds cause hypolipidemia not by enhancing the storage of peripheral lipids in adipose tissue but by preferentially increasing lipid utilization in the liver. Glyphosate caused no peroxisome proliferation or hypolipidemia, suggesting that these effects are associated with the structural similarity between phenoxy acid herbicides and clofibrate.     

An extensive pattern of atypical neural speech-sound discrimination in newborns at risk of dyslexia

ObjectiveIdentifying early signs of developmental dyslexia, associated with deficient speech-sound processing, is paramount to establish early interventions. We aimed to find early speech-sound processing deficiencies in dyslexia, expecting diminished and atypically lateralized event-related potentials (ERP) and mismatch responses (MMR) in newborns at dyslexia risk.MethodsERPs were recorded to a pseudoword and its variants (vowel-duration, vowel-identity, and syllable-frequency changes) from 88 newborns at high or no familial risk. The response significance was tested, and group, laterality, and frontality effects were assessed with repeated-measures ANOVA.ResultsAn early positive and right-lateralized ERP component was elicited by standard pseudowords in both groups, the response amplitude not differing between groups. Early negative MMRs were absent in the at-risk group, and MMRs to duration changes diminished compared to controls. MMRs to vowel changes had significant laterality × group interactions resulting from right-lateralized MMRs in controls.ConclusionsThe MMRs of high-risk infants were absent or diminished, and morphologically atypical, suggesting atypical neural speech-sound discrimination.SignificanceThis atypical neural basis for speech discrimination may contribute to impaired language development, potentially leading to future reading problems.